ArticlePsychopharmacology2026
Marked sex differences are observed in heroin acquisition and affective states in rats but converge to similar levels of footshock stress-induced reinstatement.
Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- GABAergic neurons in the ventrolateral periaqueductal gray mediate fentanyl withdrawal and self-administration in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Robust effects of food deprivation as a relapse trigger: comparison to other stressors, and investigation of predictive individual traits in male and female rats.Psychopharmacology · 2026Article
- Impact of sex on heroin intravenous self-administration by heterogeneous stock rats.Psychopharmacology · 2026Article
- Involvement of the dorsal raphe serotonin system in basal and punished heroin self-administration and stress-induced reinstatement in male and female rats.Psychopharmacology · 2026Article
- Impact of Age on Heroin Intravenous Self-Administration in Wistar Rats.bioRxiv : the preprint server for biology · 2026Article
- Impact of Sex on Heroin Intravenous Self-Administration by Heterogeneous Stock Rats.bioRxiv : the preprint server for biology · 2026Article
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Authors and funding
4 authors.
Funding
Abstract
rationaleNegative affective states, particularly those driven by stress, are known to trigger the development of opioid addiction and relapse. Previous preclinical research has identified sex differences in vulnerability to stress and resulting compulsion to consume drugs.
objectivesTo investigate sex differences in heroin self-administration, stress-induced reinstatement, and related affective state in rats.
methods22- and 50-kHz ultrasonic vocalizations (USVs), reflecting negative and positive affective state, respectively, were recorded during a heroin self-administration and footshock stress-induced reinstatement model in Sprague-Dawley rats. We hypothesized that females would display increased vulnerability towards heroin use disorder-like profiles.
resultsFemales showed elevated acquisition of heroin self-administration, but behavioral patterns were not linked to gonadal hormone levels. During heroin acquisition, males emitted significantly more 50 kHz calls compared to females, suggesting positive reinforcement-driven intake. We observed successful stress-induced reinstatement in both sexes, with males and females reaching similar overall numbers of active lever presses by the end of the reinstatement session. However, they appear to do so via different strategies, with females displaying "frontloading", rapidly lever pressing in the first 20 min of the behavioral session, perhaps indicating differential stress vulnerability or differences in underlying neural encoding of stressor/reward value. Successful stress-induced reinstatement in both sexes is accompanied by a distinct pattern of USVs, whereby a high number of anticipatory 50 kHz calls are emitted prior to the onset of reinstatement sessions, followed by 22 kHz call production by males during reinstatement sessions, perhaps reflecting drug seeking to relieve negative affect or negative affective responses to drug unavailability.
conclusionsThese findings indicate sex-specific vulnerabilities to development of heroin use disorders.
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